We are using the non-defective parvovirus MVM as a means of identifying tumor cell functions active during S phase. We are particularly interested in studying those cellular functions required for viral DNA synthesis which are expressed in certain tumor cell lines, but are absent in others. MVM is a "cytotropic" virus. It is able to replicate in some tumor cell lines but is unable to replicate in others. One important aspect of this specificity appears to be due to a differentiation-dependent cell function necessary for a critical early step in viral DNA synthesis. We have identified an active viral DNA replication complex. Using this complex as the basis for an assay, we propose to subfractionate tumor cell extracts to identify 1) functions present in specific tumor cells necessary for viral DNA synthesis and 2) assay for possible virus coded functions involved in viral DNA replication. The formation of such viral gene products will be studied in permissive and non-permissive tumor cell lines.